Cell Injury: Sub-lethal and Lethal Injury Flashcards
Does the need for blood supply change in cell when performing exercise?
Yes! Significantly! The harder the exercise, the higher the demand for blood.
Cause of Cell Death - Ischemia
Insufficient blood supply die to decrease in blood flow or increased metabolic function.
Hypoxia
Partial obstruction of O2
Anoxia
Complete obstruction of O2
Drowning
Obstruction of the respiratory tree
Pneumonia
Inadequate O2 transport across lung surface
Anemia
Lack of RBCs to transport O2 in the blood
CO Poisoning
Inability of cell to use O@ for cellular respiration
What happens with decreased blood flow?
Decreased O2 supply, changes metabolism from aerobic to anaerobic
Decreased ATP synthesis changes cell membrane permeability and can lead to intracellular movement of ions and fluids. Results in cell swelling (Na+ comes in and brings water with it) and affects cellular homeostasis.
Increased build up of O2
Results in cell death (necrosis) if not reversed
Causes of Cell Death - Infecting Agents
Bacteria and Viruses
Exotoxin
- Come inside and secrete something
- Ex: Snake bite with venom
Endotoxin
-Cell wall gets destroyed, wall has toxins inside of it which go to other areas of the body and cause issues.
Infecting agents can cause inflammation/immune reactions of the body that damages cells/tissues
Example of Exotoxins (2)
Botulinum: Destroys SNARE proteins (can’t bring ACh in)
Tetani: Blocks GABA and glycine NTs - inhibitory NTs
Leads to increased muscle contractions in both examples
Example of Endotoxin
Sepsis: Loss of plasma volume, hypovolemic, endothelial cell damage
What are the two ways viruses can kill?
Direct and Indirect
Direct Crytopathic effect: Invades and redirects cell machinery and disturb the cell
Indirect Cytopathic effect:
Hijack our DNA to make RNA by going into cell changing the enzyme to create DNA to RNA that’s sent out and causes injury
Viral proteins insert on the cell membrane -> form pores -> alter cell permeability -> cell swelling and death
Viral proteins integrate into cellular genome -> produces foreign proteins -> encodes proteins are expressed on the cell surface -> T lymphocytes recognize this foreign protein -> attacks and destroys host cells
Cause of Cell Injury - Immune Reactions
Cell injury -> Antigen -> Inflammatory Cells ( Neutrophils, Macrophages, T and B Lymphocytes) -> IgE antibodies on the surface of Mast and Basophils (releases histamines)
Mild reaction: Runny and watery eyes
Moderate to severe: Bronchoconstriction
Cross-reactivity between foreign antigen and host antigen
-Something nonself and self
Chronic persistence of foreign antigens
-Chronic inflammatory reaction
Sensitization to endogenous antigens (Type 1 DM)
-Viral infection -> islet antigens -> destruction of islet cells by T cells
Cell Injury - Chemical Factors
Directly injure cells: Mercury
Metabolically transformed into toxic agents - acetaminophen
Oxygen toxicity phenomenon: Normal cellular metabolism for energy produces free electrons (steals electron from healthy cells) + oxygen + hydrogen for stability = ROS
What is ROS?
Reactive Oxygen Species
Factors that likely increase oxygen toxicity
Prolonged and intense exercise (sedentary), prolonged exposure to high levels of oxygen, UV light, pollutants, tobacco smoke, poor nutrition
Conditions: HEart Disease, CVA, Diabetes mellitus, Parkinsons Disease, Alzheimers, Premature aging and cancer
Are all radicals bad?
No! Some are positive helping fight inflammation, kill bacteria, regulate ANS
Enzymes in cells converts radicals back to usable oxygen
Ex: Nitric Oxide is good!
Why are antioxidants important?
Neutralize free radicals and protects cells/DNA from damages
Endogenous and Exogenous
What are some benefits from NO?
Long term memory
Increases cell membrane permeability (easy crossing of ACh)
Helps GI mucosa
Inhibits virally induced cytokine and chemokine production
Stimulates collagen synthesis
Anti-lipid: coats blood vessels
-Helps prevent platelet adhesion and promotes fibrinolysis
Exercise and Free Radicals
Moderate, regular long-term aerobic exercise protects DNA damage
Increase formation of NO
Up-regulation of endogenous antioxidants
FITT
Frequency
Intensity
Time
Type
What is the recommended exercise dosage?
At least 150 min of moderate-intensity aerobic activity
At least 2 days of muscle-strengthing activity
Causes of Cell Injury - Genetic Factors
Alterations in structure or number of chromosomes
Causes of Cell Injury - Mechanical Factors
Physical stress theory
Changes in the relative level of physical stress cause a predictable adaption
Typical Response:
Death
Injury
Maintenance
Atrophy (Decreased Stress Tolerance)
Hypertrophy (Increased Stress Tolerance)
Cell Injury - Nutritional Factors
- Nutritional Imbalances – abnormal vitamins and mineral
- Lack of essential amino acids affects protein synthesis
- Deficiency: Protein malnutrition (Kwashiorkor), Marasmus (generalizaed deficency)
- Excessive: Obesity
- Decreased iron – leads to anemia
- Increased iron (hemochromatosis) - forms free radiaclas and damages cell/tissues/organs
- Think about athletes and iron deficiency/excess iron
- Female athletes and menstration
Fatty Liver
- Alcohol: Liver produces lots of lipids and no protein lead to injury
- Proteins are needed to transport fat in the blood from liver
- Increase in intracellular lipid accumulation within hepatocytes as tissues overload or form various metabolites
CI - Physical Injuries
- Trauma – motor vehicles accidents and penetrating trauma by weapons – prolonged rehabilitation
- Extremes of physical agents:
- Temperature: Hypothermia and hyperthermia
- Electricity
- Irradiation
- Radiolysis of water and production of hydroxyl radicals -> membrane damage and breakdown of structural and enzymatic proteins results in cell death
- Damage to arterioles -> inadequate blood supply (ischemia) to irradiated tissues
- Damage to nucleic acids leads to gene mutations
CI - Psychosocial Factors
Fear, tension anxiety – influence individual threshold for tissue adaptation and injury
Occasionally satisfied or unsatisfied work environment -> higher risk of injury
Cellular Aging
Aging and Aging-related changes significantly affect homeostasis and the recovery process
>300 theories to explain cellular aging
Telomere aging clock
Telomere on chromosomal end decreases. Without telomere the cell dies.
Trying to stop this process may lead to cancer
Cell Injury
Ionic shifts across cell membrane with increased sodium and calcium influx into cell
Increased cell volume (swelling) in cytosol – mitochondria, ER
Increased lactic and anerobic metabolism, increased pH
Go from anerobic to aerobic system
Don’t reduce stress leads to death
Cellular Adaptations - Atrophy
- Atrophy – reduction in cell size (not number) and organ size
- Other Examples: Muscle wasting, bone loss, spinal atrophy in spinal cord injury
- Cachexia in cancer die to diet and malnutrition
- Loss of muscle and fat
- Focus on doing what patient can do at that time, don’t push them
CA – Hypertrophy
- Hypertrophy – increase in cell size and organ size
- Pure hypertrophy occurs in striated muscles (heart and skeletal muscles)
- Ex: Left ventricle hypertrophy
- Hypertension due to increased blood pressure causes hypertrophy
- Pure hypertrophy occurs in striated muscles (heart and skeletal muscles)
CA-Hyperplasia
- Hyperplasia – increase in number of cells -> organ size
- Ex: Caluses on hands from weight lifting
- Pure hyperplasia: endometrial thickness and callus
- Hypertrophy and hyperplasia occur together in prostate enlargement, obstruction of the urethra and bladder
Metaplasia
- Metaplasia – change in cell morphology and function. One adult cell type to another
- Ex: Smoking
- Changes from ciliated psuedostratisfied columnar to stratisfies squamous epithelium
- Leads to thickening of respiratory epithelium
- If smokers stop cells can regenerate back to normal
- Changes from ciliated psuedostratisfied columnar to stratisfies squamous epithelium
- Ex: Smoking
Dysplasia
- Increase in cell numbers, altered cell morphoplogy and loss of histologic organization
- Usually seen in cancer patient
- Neoplasia and aplasia
- Neoplasia: Cancer
- Aplasia: Cell is abnormal; Origin is unknown
Can the cell revert to normal?
If the nucleus is not damages
Remove stress
Restore energy source
Restore ion balance
Necrosis
- Necrosis: Cell Death when exposed to uncontrolled extreme conditions
- Internal cellular environment leads to complete discord to cell functioning
- Wall or membrane of cell
- Leads to inflammation
- Disintegration
- Passive, No energy required
- Enlarged
- Lysosomes and mitochondria release cells that lead to cell death
- Mitochondria
- Leads to aerobic to anerobic shift
- Mitochondria
Apoptosis
- Apoptosis: Preplanned cell death, cell takes part in its death
- Die naturally, Ex: RBCs live for 120 days
- If cells don’t die on time leads to cancer
- Cells die to fast leads to heart disease, liver disease, AIDs
- No disintegration
- Shrinkage of cell
- Requires Energy
Hallmarks of Lethal Injury
- Nucleus
- Mitochondria: decreased ATP and energy production
- Lysosomes: decrease digestive enzymes after death
- Dead cells are released into ECF and then into circulation (clinical markers of injury)
- Biomarkers can be released in system and tested to see if there are issues
- Ex: C-Reactive Protein
Coagulative (Dry Gangrene)
- Coagulative (dry gangrene) - several days after cell death
- Ischemia
- Liver
Liquefactive (wet gangrene)
Liquefactive (wet gangrene) - within hours of cell death
Bacteria
Brain
Gangrenous Necrosis
Extremities
Caseous Necrosis
TB
Granuloma
Protective cells make a wall around bacteria
Fatty Necrosis
Abdomen region
Fibrinoid necrosis
Trauma in blood vessel wall
Gas Gangrene
Pathogen: Clostridium Perfringens
Blisters with gas bubbles of the affected area, fever, pain, increased Hr/breathing
Ex: Surgery, cellulitis, fasciitis
